The extracellular matrix protein βIG-H3 is expressed at myotendinous junctions and supports muscle cell adhesion

Molecules of the extracellular matrix (ECM) play important roles in the development and maintenance of myotendinous junctions (MTJs), specialized regions of muscle to bone union. In this report we provide evidence that skeletal muscle cells synthesize the collagen- and fibronectin-binding ECM protein βIG-H3 and that βIG-H3 is localized to MTJs. In situ hybridization experiments revealed that during E16.5–E18.5 of murine development, βIG-H3 RNA transcripts were expressed where developing skeletal muscle fibers contact primordial cartilage and bone. Immunohistochemical analysis verified that the βIG-H3 protein itself localized distinctively at MTJs, and ultrastructural analysis suggested that βIG-H3 associates with extracellular fibers and the surface of cells. In vitro, recombinant βIG-H3 functioned as an adhesion substratum for skeletal muscle cells. Adhesion was significantly reduced by anti-integrin α7 and β1 antibodies, suggesting that βIG-H3 binds to skeletal muscle cells via α7β1 integrin. Localization of βIG-H3 to the termini of skeletal muscle fibers and the binding of βIG-H3 to cells and to molecules of the ECM suggests that βIG-H3 may play an organizational and structural role in developing MTJs, linking skeletal muscle to components of the ECM.